The long-term goal of this application is to establish at Howard University, an historically African American institution, a strong molecular genetics research program. The program envisioned will greatly enhance research at the Howard University College of Medicine in the area of genetic hemoglobin disorders. The program will focus on basic research needed for a greater understanding of the hemoglobinopathies at the molecular genetics level and for the eventual design of DNA-based treatment strategies. Examples of research areas and capabilities desirable for the program are: regulation of gene expression, site-directed mutagenesis, gene transfer, and gene conversion via oligonucleotide technology. The planned research program will complement basic and clinical studies already on-going at the Howard University Center for Sickle Cell Disease. The program will also benefit other College of Medicine units currently engaged in molecular research related to cardio-vascular and lung disorders. During the first one and one-half year phase of this application, an Advisory Committee will be formed. It will consist primarily of investigators from institutions already conducting research on the molecular biology of hemoglobin. In collaboration with an NHLBI staff member, who will be also a Committee member, this group will help identify and recruit an accomplished research scientist with demonstrated leadership in the molecular genetics areas listed above. The committee will also provide advice to the recruited scientist in the development of a six-year research plan. During the second six-year phase, the recruited scientist will implement the program as principal investigator. After support from this grant ends, the recruited scientist will continue as molecular genetics program director and will qualify for a leadership research position at the College of Medicine.